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Active movement of T cells away from a chemokine

Nature Medicine volume 6, pages 543–548 (2000)Cite this article

Abstract

Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokine stromal cell derived factor-1 (SDF-1). There was selective repulsion of subpopulations of T cells at high concentrations of recombinant SDF-1 or naturally occurring bone marrow-derived SDF-1, which could be inhibited by pertussis toxin and antibody against the chemokine receptor CXCR4. Distinct sensitivity profiles to genistein, herbimycin and 8-Br-cAMP biochemically distinguished movement of cells towards or away from an SDF-1 gradient. In vivo, antigen-induced T-cell recruitment into the peritoneal cavity was reversed by high but not low concentrations of SDF-1. The phenomenon of movement away from a chemokine represents a previously unknown mechanism regulating the localization of mature T cells. It adds to the functional repertoire of chemokines that may participate in immune physiology and may be applied therapeutically to alter the immune response.

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Figure 1: SDF-1 induces cell movement towards and away from a chemokine concentration gradient.
Figure 2: Digitized time lapse photography of cells moving in the presence of a gradient of SDF-1.
Figure 3: Movement towards and away from SDF-1 has different sensitivities to inhibitors and cyclic nucleotide agonists.
Figure 4: Checkerboard analysis of T-cell chemotaxis in response to BMCM.
Figure 5: SDF-1 at high concentrations abrogates inflammatory infiltration in vivo.

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Authors and Affiliations

  1. AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, 02129, Massachussetts , USA

    Mark C. Poznansky, Ivona T. Olszak, Russell Foxall, Richard H. Evans, Andrew D. Luster & David T. Scadden

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  1. Mark C. Poznansky
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Correspondence to David T. Scadden.

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Poznansky, M., Olszak, I., Foxall, R. et al. Active movement of T cells away from a chemokine. Nat Med 6, 543–548 (2000). https://doi.org/10.1038/75022

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